EP2349281A1 - Composition comprising a glycoside of a mono- or diacyiglycerol compound and an oil rich in n-3 polyunsaturated fatty acids, a method of producing the composition and use of the composition - Google Patents
Composition comprising a glycoside of a mono- or diacyiglycerol compound and an oil rich in n-3 polyunsaturated fatty acids, a method of producing the composition and use of the compositionInfo
- Publication number
- EP2349281A1 EP2349281A1 EP20090752271 EP09752271A EP2349281A1 EP 2349281 A1 EP2349281 A1 EP 2349281A1 EP 20090752271 EP20090752271 EP 20090752271 EP 09752271 A EP09752271 A EP 09752271A EP 2349281 A1 EP2349281 A1 EP 2349281A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- composition according
- composition
- oil
- daily dose
- octadeca
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7032—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a polyol, i.e. compounds having two or more free or esterified hydroxy groups, including the hydroxy group involved in the glycosidic linkage, e.g. monoglucosyldiacylglycerides, lactobionic acid, gangliosides
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/115—Fatty acids or derivatives thereof; Fats or oils
- A23L33/12—Fatty acids or derivatives thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/56—Materials from animals other than mammals
- A61K35/60—Fish, e.g. seahorses; Fish eggs
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/31—Brassicaceae or Cruciferae (Mustard family), e.g. broccoli, cabbage or kohlrabi
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
- A61K36/535—Perilla (beefsteak plant)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/55—Linaceae (Flax family), e.g. Linum
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
- A61K36/738—Rosa (rose)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Definitions
- composition comprising a glycoside of a mono- or diacyiglycerol compound and an oil rich in n-3 polyunsaturated fatty acids, a method of producing the composition and use of the composition
- This invention relates to a composition of a glycoside of a mono- or diacyiglycerol compound, preferably retrieved from a plant material, and an oil rich in n-3 polyunsaturated fatty acids and the use thereof for the treatment of or prevention of inflammatory diseases such as, but not limited to pain and stiffness in joints associated with e.g. osteoarthritis.
- Patent No. 6,024,960 a rose hip formulation for use as an anti- inflammatory natural medicine is described.
- WO 03/043613 A1 relates to the use of a glycoside of a mono- or diacyiglycerol compound for the treatment of inflammatory diseases, and more particularly to the compound 3- ⁇ -D-galactopyranosyloxy-2-(octadeca- 9Z, 12Z, 15Z-trienoyloxy)propanyl octadeca-9Z, 12Z, 15Z-trienoate (also known as GOPO, which is a registered trademark) either obtained from natural sources, such as rose hips (the fruits of Rosa Canina) or prepared by total synthesis.
- the action of this compound was shown to be alleviating chemiluminiscence of polymorphnuclear leucocytes and chemotaxis of mononuclear leucocytes.
- WO 2008/003314 A1 describes another method of isolating a glycoside of a mono- or diacylglycerol compound from a plant material, and to products obtained therefrom.
- the document relates to the isolation of and products comprising 3- ⁇ -D- galactopyranosyloxy- 2 - (octadeca- 9Z, 12Z, 15Z - trienoyloxy) propanyl octadeca - 9Z, 12Z, 15Z - trienoate, in particular from a rose hip material.
- Fish oil is also a known material that has some beneficial effects.
- n-3 polyunsaturated fatty acids (PUFA) of dietary fish oil are known to reduce the level of triglycerides and very low density lipoprotein cholesterol. Dietary supplementation by, for example, 1.0 ml capsules of fish oil containing about 0.3 g of the primary n-3 PUFA, eicosapentaenoic acid (EPA) and docosahexanoic acid (DHA), have been used, though other concentrations of the PUFAs in supplements are available, ranging for example from 20 to 50% by weight.
- EPA eicosapentaenoic acid
- DHA docosahexanoic acid
- Osteoarthritis is characterized by an erosion of articulated cartilage which becomes soft, frayed and thinned with eburnation of subchcondral bone and outgrowths of marginal osteophytes. Pain and loss of function is the result. This is more common in older persons and is considered a degenerative joint disease which mainly affects the weight bearing joints such as the hips and knees. While inflammation is one symptom of arthritis, the pain and stiffness of the joints are particularly debilitating as this physically inhibits activity and lessens the motivation for daily activities, as well as causes sleeplessness, and results in an overall negative impact on the general well being of an individual, as one susceptible to such pain and joint stiffening must generally refrain from normal daily activities such as walking, entering a vehicle, etc.
- glycosides of a mono- or diacylglycerol compound have shown to lack stability in aqueous solutions as described in WO03/43613, and tend to degrade during storage. This leads to a decrease in the concentration of the active ingredient in the composition during storage and difficulties in determining whether the dose given to the patient is correct.
- inflammatory conditions such as, but not limited to hepatitis, meningitis, rheumatoid arthritis, inflammatory bowl diseases, such as Crohns disease, allergic syndromes, diabetes, congestive heart disease, psoriatic, reactive or osteo-arthriti
- compositions comprising a glycoside of a mono- or diacylglycerol compound and an oil rich in n-3 polyunsaturated fatty acids.
- the inventors Based on the knowledge that the glycosides of mono- or diacyl glycerol compounds possess antiinflammatory activity, the inventors have developed a composition based on a glycoside of a mono- or diacylglycerol compound and an oil rich in n-3 polyunsaturated fatty acids.
- composition may preferably further comprise a rose hip concentrate and optionally other ingredients, e.g. antioxidants.
- composition according to the invention comprises GOPO and a n-3 PUFA rich oil, especially fish oil, shark oil, seal oil, whale oil or other sea living mammals or animals, and linseed oil, rapeseed oil, chia seed oil, kiwifruit seed oil, perilla seed oil, cowberry seed oil and mixtures thereof.
- composition shows improved stability of GOPO compared to the aqueous solution described in WO 03/043613 A1 , without compromising on the anti-inflammatory synergistic effect related to especially joint diseases of the rose hip extract and the fish oil described in EP 1337263 Bl Since the compositions according to the invention show an improved stability of GOPO, which leads to a reduction of the degradation of GOPO during storage of the composition, it is easier to determine whether the patients are given the correct dose of GOPO in order to achieve the anti inflammatory effect in the patients in comparison with the known less stable aqueous solution.
- compositions containing fish oil and rose hip extract alone are easier to standardise the compostion according to the invention comprising the glycosides of mono- or diacylglycerol compounds and the oil rich in n-3 PUFA, e.g. fish oil, compared to standardising a composition containing fish oil and rose hip extract alone.
- glycosides of mono- or diacylglycerol and similar terms are intended to mean a class of glycosides of mono- or diacylglycerols (as well as ethers), such as those which may be isolated from plants e.g. as illustrated by the methods described in WO 2008/003314 A1 or WO 03/043613 A1 , and which are not esters of eicosapentaenoic acid.
- the "glycoside” part is typically a pentose, hexose or heptose, in particular hexoses such as galactose and glucose, e.g.
- glycosides of mono- or diacylglycerol product relates to a product obtained from a plant material comprising a glycoside of mono- or diacylglycerol compound.
- the glycosides of mono- or diacylglycerol product may be obtained from the plant material by isolation by means of chromatography, microfiltration, filtration, centrifugation, extraction or any combination thereof.
- glycosides of mono- or diacylglycerol compound may have the formula I:
- R and R' are independently selected from hydrogen, C10-24 alkyl, and C10-24 acyl, said alkyl and acyl groups having 0 to 5 unsaturated bonds, and R1 , R2, R3 and R4 are independently selected from hydrogen and glycoside moieties; with the first proviso that not both of R and R' are hydrogen, and with the second proviso that none of R and R 1 is eicosapentaenoyl.
- the anti-inflammatory agent may also be present in the furanose form (or a mixture of the pyranose and furanose forms) as a solid and in solution.
- C10-24 alkyl is intended to mean a linear or branched hydrocarbon group having 10 to 24 carbon atoms, e.g., decyl, undecyl, dodecyl, tetradecyl, hexadecyl, octadecyl, nonadecyl, eicodecyl, etc.
- the alkyl and acyl groups may have 0 to 5 unsaturated bonds such as double or triple bonds, in particular double bonds.
- acyl groups having one or more unsaturated double bonds are the residues of palitoleic acid (C16:1), oleic acid (C18:1), linoleic acid (C18:2), linolenic acid (C18:3), arachidonic acid (C20:3), retinoic acid (C20:5), etc.
- glycosides of mono- or diesters (or ethers) of glycerol are diesters, diethers, or monoether-monoesters, i.e. R and R 1 are independently selected from C10-24 alkyl and C10-24 acyl.
- the currently most preferred glycosides are glycosides of diesters, i.e. R and R 1 are independently C10-24 acyl.
- the alkyl and acyl groups have 0 to 5 unsaturated bonds.
- any alkyl and acyl groups having 0 to 4 unsaturated bonds such as 1-3 unsaturated bonds, e.g. 2 or 3 unsaturated bonds, in particular 3 unsaturated bonds, are the most suitable ones as R and R 1 .
- any unsaturated bonds preferably are double bonds.
- particularly interesting antiinflammatory agents are those where R and R' are both C16-20 acyl having 1 to 3 double bonds, such as C18 acyl having 3 double bonds, in particular where the "sugar” moiety is glucose or galactose, in particular galactose.
- R1 , R2, R3 and R4 are independently selected from hydrogen and glycoside moieties, preferably at the most only one of R1 , R2, R3 and R4 is a glycoside moiety.
- the latter embodiment relates to compounds that are often found in vegetable sources along with compounds where all of R1 , R2, R3 and R4 are hydrogen. In some interesting embodiments, all of R1 , R2, R3 and R4 are hydrogen.
- glycoside moieties is intended to mean a mono- or disaccharide moiety, e.g. derived from O-galactopyranose, O- glucopyranose, O-galactopyranosylgalactopyranose, O- glucopyranosylgalactopyranose, O-galactopyranosylglucopyranose and O- glucopyranosylglucopyranose.
- glycoside of a mono- or diacylglycerol compound preferably has the formula II:
- R, R 1 , R1 , R2, R3 and R4 all are as defined above. More specific examples of the glycoside of a mono- or diacylglycerol compound of particular interest are those selected from ⁇ -D- galactopyranosyl derivatives, ⁇ -D-galactopyranosyl derivatives, ⁇ -D- glucopyranosyl derivatives, and ⁇ -D-glucopyranosyl derivatives, such as ⁇ - D-galactopyranosyl and 6-O-( ⁇ -D-galactopyranosyl)- ⁇ -D-galactopyranosyl derivatives.
- glycoside of a mono- or diacylglycerol compounds are 3- ⁇ -D-galactopyranosyloxy-2-(octadeca- 9Z, 12Z, 15Z-trienoyloxy)propanyl octadeca-9Z, 12Z, 15Z-trienoate, 3- ⁇ -D- glucopyranosyloxy-2-(octadeca-9Z, 12Z, 15Z-trienoyloxy)propanyl octadeca- 9Z, 12Z, 15Z-trienoate, 3- ⁇ -D-galactopyranosyloxy-2-(octadeca-9Z, 12Z, 15Z- trienoyloxy)propanyl octadeca- ⁇ Z. ⁇ Z.I ⁇ Z-trienoate, 3- ⁇ -D- glucopyranosyloxy-2-(octadeca-9Z,12Z,15Z-trienoyloxy)
- the most preferred galactolipid is e.g. 3- ⁇ -D-galactopyranosyloxy-2- (octadeca- 9Z, 12Z, 15Z-trienoyloxy)propanyloctadeca- 9Z, 12Z, 15Z- trienoate (GOPO).
- the glycosides of mono- or diacylglycerol compounds, especially GOPO, as mentioned above, are isolated from plant material such as rose hips.
- the rose hip is preferably obtained from wild rose bushes, in particular the rose hip is selected from the group consisting of Rosa canina ("dog rose hip"), Rosa gallica, Rosa condita, Rosa rugosa, Rosa hugonis, Rosa nitida, Rosa pendulina, Rosa pimpinellifolia, and Rosa sericea.
- the plant material is not limited to rose hip only. It might consist of any plant material containing a glycoside of mono- or diacylglycerol compounds, and especially galactolipids, such as fruit, vegetables or cereals, where the fruit, vegetable or cereal is preferably selected from the group consisting of olive (e.g. Olea europaea), alfalfa (e.g. Mediargo sativa L.), soya bean (e.g. Glycine max), potato (e.g. Solanum Turerosum L.), pepper (e.g. Capsicum annuum L.), oat (e.g. Avena sativa), wall cress (e.g.
- olive e.g. Olea europaea
- alfalfa e.g. Mediargo sativa L.
- soya bean e.g. Glycine max
- potato e.g. Solanum Turerosum L.
- pepper e.g. Cap
- Arabidopsis thaliana Petunia hybrida, lyme grass (e.g. Elymus arenarius), broom (e.g. Sarothamnus scoparius), coltsfoot (e.g. Tussilago farfara), chenopodiaceae, seakale (e.g. Crambe maritima), sloe (e.g. Prunus spinosa), eryngo (e.g, Eryngium), sea purslane (e.g. Honckenya peploides), blackberry, mountain ash (e.g. Sorbus aucuparia), service tree (e.g. Sorbus domestica), sea buckthorn (e.g.
- hemp agrimony e.g. Eupatorium cannabinum
- cucumber e.g. M. charantia or M. rustrata
- Catharanthus roseus e.g. M. charantia or M. rustrata
- Catharanthus roseus e.g. M. charantia or M. rustrata
- Catharanthus roseus e.g. M. charantia or M. rustrata
- yew e.g. Taxus baccata
- mistletoe e.g. Viscum album
- horsetails e.g. Equisetum arvense
- meadowsweet e.g. Filipendula ulmaria
- dropwort e.g. F. hexapetala
- Ephidera e.g. E. sp.
- reed e.g. Phragmites communis
- ground ivy e.g.
- seaweed preferably, the seaweed is selected from the group consisting of Anfeltia tobuchiensis (Rhodophyta), Laminaria japonica, Sargassum pallidum (Phaeophyta), Ulva fenestrate (Chlorophyta), Zostera marina (Embriophyta), sea wrack (Fucus vesiculosus), green alga (Chlorella vulgaris), Cyanobacteria (e.g.
- the oil ingredient is preferably an oil naturally rich in n-3 PUFA's, and the preferred oils have a naturally high content of n-3 polyunsaturated fatty acids, especially ⁇ -linolenic acid (ALA), eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA).
- ALA ⁇ -linolenic acid
- EPA eicosapentaenoic acid
- DHA docosahexaenoic acid
- the oils rich in n-3 PUFA's are normally of animal or vegetable origin.
- oils rich in n-3 PUFA's of animal origin are seal oil (family: Phocidae), whale oil (family: Cetacea) or other sea living mammals or animals and fish oil originating from oily fish species, e.g. cold water fish such as codfish (especially codfish liver oil), salmon, herring, mackerel, sardines, sand lances/sand eels or anchovies, although other species of oily fish, e.g. tuna or shark may be used.
- examples of n-3 PUFA's rich oils of vegetable origin are linseed oil (Linum usitatissimum), rapeseed oil (e.g. Brassica napus L. or B.
- campestris L chia seed oil (Salvia hispanica), kiwifruit seed oil (Actinidia chinensis), perilla seed oil (Perilla frutescens), cowberry/lingonberry seed oil (Vaccinium vitis-idaea) and mixtures thereof.
- the oil ingredient which is a natural substance, may vary in its concentration of n-3 PUFA's. Thus, the amount constituting a unit dose may vary in relation to the concentration of the fatty acids.
- fish oil which is a preferred n-3 PUFA rich oil
- concentration of n-3 PUFA's the higher unit daily dosage should be administered, i.e., five capsules at 10% would be equivalent to one capsule at 50%. This may, of course, vary with the type of fish used to obtain the fish oil and the processing used to produce the fish oil component, which techniques are conventional in the art.
- cod fish oil may have about 20% of the n-3 PUFA's while other species may have more or less and this amount may be further concentrated using appropriate conventional processing steps.
- the most common fish oil supplement is in the form of 1.0 ml capsules, containing about 0.3 g of PUFA's per capsule, though capsules containing up to 50 % PUFA's are commercially available.
- the fish oil may be obtained in a dry powdered form.
- a dry powder containing 25% by weight of fish oil is commercially available, one such powder containing 25.7 % n-3 18:22 fish oil, having from about 41.0 to 42.2 mg/g EPA as triglycerides and from about 27.0 to 28.8 mg/g DHA calculated as triglycerides.
- Such a material is well suited for use in accordance with the present invention.
- the composition may also contain rose hip extract, which is a naturally occurring source for the glycoside of mono- or diacylglycerol compounds mentioned above.
- the rose hip is preferably obtained from wild rose bushes, in particular the rose hip is selected from the group consisting of Rosa canina ("dog rose hip"), Rosa gallica, Rosa condita, Rosa rugosa, Rosa hugonis, Rosa nitida, Rosa pendulina, Rosa pimpinellifolia, and Rosa sericea.
- the rose hip extract is in powdered form and may be pelletized or placed in capsules with a physiologically acceptable carrier for formulation into unit dosages.
- a unit dosage comprises a therapeutically effective daily amount of the glycosides of mono- or diacylglycerol compounds, the oil rich in n-3
- PUFA's and optionally the rose hip extract which may be taken as a single daily administration or by multiple small doses taken over the course of a day.
- composition according to the invention can be formulated for delivery via various routes of administration. Oral administration is preferred for ease of use.
- a unit dosage can comprise a therapeutically effective amount of the combination of a glycoside of a mono- or diacylglycerol compound and the oil rich in n-3 PUFA's for a single daily administration (e.g. orally or by feeding tube in an enteral diet for example), or be formulated to provide multiple doses per day.
- a unit dosage will depend on many factors, including age, condition, and disease state, but in any event, the entire daily dosage will be that which is physiologically acceptable to the individual and may be administered daily over a prolonged period of time, as joint diseases are normally chronic illnesses.
- the dose of the anti- inflammatory agent which would be effective in the treatment of the inflammatory condition, in particular arthritis and osteoarthrosis, and relief of the symptoms associated therewith, is currently under investigation. Based on previous results using rose hip extracts for the treatment of arthritis and osteoarthrosis, it is believed that a dosage will be in the range of 0.00150 mg/kg body weight per day, such as 0.005-20 mg/kg body weight per day (mg/kg/day) of the isolated glycoside of mono- or diacylglycerol, especially but not limited to GOPO.
- a similar to lesser dose rate could be administered on a daily basis as a prophylactic dose.
- the medicament may be in the form of a daily dose form applicable for administration of it in a dose from about 0.001 to about 50 mg/kg body weight per day and preferably 0.005-20 mg/kg body weight per day or 0.01 - 500 mg per day of the isolated glycoside of mono- or diacylglycerol, such as GOPO in unitary or multiple doses, the user taking e.g. from one to four capsules per day.
- a daily dose form applicable for administration of it in a dose from about 0.001 to about 50 mg/kg body weight per day and preferably 0.005-20 mg/kg body weight per day or 0.01 - 500 mg per day of the isolated glycoside of mono- or diacylglycerol, such as GOPO in unitary or multiple doses, the user taking e.g. from one to four capsules per day.
- a unit daily dose of n-3 PUFA rich oil, such as fish oil, in accordance with the present invention should be in the range of about 500-3600, more preferably 1300-2600 mg of the n-3 PUFA containing fish oil per day in either a single dose or in multiple smaller doses, so as to provide from about 0.1 to 1.8 g PUFA's per day, more preferably about 0.1 to 0.8 g PUFA's per day.
- a preferred unit dosage of the optionally added rose hip extract ingredient will be from about 0.02 to about 0.3 g/kg body weight per day or about 1.5 to 30 g per day. About 2.5 to 15 g per day are preferred, and about 2.5 to 6.0 g are most preferred. A similar to lesser dose rate could be administered on a daily basis e.g. as a prophylactic dose.
- a preferred unit dosage of the optionally added rose hip extract ingredient will be from about 0.01 to about 0.3 g/kg body weight per day or about 0.75 to 30 g per day. About 0.75 to 6 g per day are preferred, and about 1.0 to 3.0 g are most preferred as a lesser dose.
- the fish oil and the rose hip extract both contain naturally occurring antioxidants, for example Vitamin E (present in fish oil) and vitamin C (present in rose hip extract).
- Vitamin E present in fish oil
- vitamin C present in rose hip extract
- the inventors have found that a composition containing these naturally occurring antioxidants, and especially the Vitamin E in the fish oil optionally in combination with vitamin C in a rose hip extract, appear to reduce degradation of the glycerides of mono- or diacylglycerol compounds such as GOPO in the composition. Therefore, it is normally not necessary to add additional antioxidants if fish oil is used as n-3 PUFA rich oil in the composition, which optionally also contains rose hip extract. If one or more of the ingredients, i.e.
- the preferred supplementary anti-oxidants are e.g. an antioxidant selected from Vitamin C and derivatives thereof, Vitamin E, flavonoides, phenolic acids such as methyl, ethyl or n-propyl p- hydroxybenzoate, carotenes, butylated hydroxyanisoles, butylated hydroxytoluenes, nordihydroguaiaretic acid, etc. This is particularly relevant when the anti-inflammatory agent comprises one or more unsaturated bonds such as double bonds, which renders the compound susceptible to oxidative degradation.
- a preferred composition contains about 500-3600, more preferably 1300-2600 mg of the n-3 PUFA containing fish oil and 0.001 to about 50 mg/kg/day and preferably 0.005-20 mg/kg body weight per day or
- GOPO 0.01 - 500 mg of GOPO in a daily unitary dose or multiple doses, the user taking e.g. from one to four capsules per day.
- Another preferred composition contains about 500-3600, more preferably 1300-2600 mg of the n-3 PUFA containing fish oil and 0.001 to about 50 mg/kg/day and preferably 0.005-20 mg/kg body weight per day or 0.01 - 500 mg of GOPO and a rose hip extract of about 2.5 to 15 g per day and preferably about 2.5 to 6.0 g (corresponding to a daily dose of 0.02 to about 0.3 g/kg body weight per day of rose hip extract) in a daily unitary dose or multiple doses, the user taking e.g. from one to four capsules per day.
- compositions e.g. for prophylactic use, contains less rose-hip concentrate.
- This composition contains about 500-3600, more preferably 1300-2600 mg of the n-3 PUFA containing fish oil and 0.001 to about 50 mg/kg/day and preferably 0.005-20 mg/kg body weight per day or 0.01 - 500 mg of GOPO and rose hip extract ingredient will be from about 0.01 to about 0.3 g/kg body weight per day or about 0.75 to 30 g per day. About 0.75 g to 6 g per day are preferred, and about 1.0 to 3.0 g are most preferred (corresponding to a daily dose of 0.01 to about 0.3 g/kg body weight per day of rose-hip extract) in a daily unitary dose or multiple doses. Due to the reduced amount of rose hip extract in the unitary daily dose the volume thereof will be reduced and the user takes a reduced number of capsules per day, compared to the above-mentioned composition.
- the composition may be prepared as a solid powder using a dry powdered form of the oil rich in n-3 PUFA's, e.g. fish oil, as mentioned above in combination with solid GOPO.
- the rose hip extract may also be added as a solid powder.
- the rose hip extract powder may optionally be combined with GOPO, thus producing a GOPO enriched rose hip extract, before mixing with the fish oil powder. It is especially preferred to use a powdered dry form of fish oil or other n-3 PUFA rich oil, if GOPO and optionally rose hip extract are present as solids. This improves the stability of the product even further.
- the solids are also easier to transport in bulk and are more easily processed into the final product such as tablets or capsules.
- the composition may be prepared as a suspension of solid glycerides of mono- or diacylglycerol compounds such as GOPO in the oil rich in n-3 PUFA's.
- solid rose hip extract is present in the composition, it may be enriched with the glycerides of mono- or diacylglycerol compounds such as GOPO, before mixing with or suspension in the oil or powder rich in n-3 PUFA's.
- the glycerides of mono- or diacylglycerol compounds such as GOPO, which is soluble in water, may be added to the oil rich in n-3 PUFA's as an aqueous solution and thus forms an emulsion using conventional physiologically accepted emulsifiers.
- the composition according to the invention may be manufactured into tablets, capsules, caplets, elixirs, enteral formulations or be incorporated into slow release carriers, where the solid composition as described above, is particularly suitable for being incorporated into tablets, capsules, caplets and slow release carriers.
- composition may further comprise conventional physiologically acceptable carriers and/or adjuvants.
- physiologically acceptable carriers would also include other oils, oil emulsions, alcohol, etc.
- composition may also contain one or more other additional ingredients, which are used in the prophylaxis and/or treatment of e.g. joint diseases or other inflammatory conditions than those mentioned above, e.g. glucosamine, turmeric and/or ginger root extracts and optionally Vitamin D in combination with Calcium etc.
- additional ingredients which are used in the prophylaxis and/or treatment of e.g. joint diseases or other inflammatory conditions than those mentioned above, e.g. glucosamine, turmeric and/or ginger root extracts and optionally Vitamin D in combination with Calcium etc.
- the composition according to the invention may be used for the prevention, treatment or alleviation of in- flammation, whether caused by illness or medical conditions, such as viral or bacterial diseases (commonly termed "inflammatory conditions").
- Inflammation is defined in Stedman's Medical Dictionary, 26th Edition as "a fundamental pathologic process consisting of a dynamic mixture of cyto- logical and chemical reactions that occur in the affected blood vessels and adjacent tissue in response to injury or abnormal stimulation caused by physical, chemical or biological agent, including the local reactions and resulting morphologic changes, the destruction of removal of the injurious material, and the responses that lead to repair and healing".
- inflammatory conditions are hepatitis, meningitis, rheumatoid arthritis, inflammatory bowl diseases such as Crohn's disease, allergic syndromes, diabetes, congestive heart disease, psoriatic, reactive or osteoarthritis or other arthritides such as osteoarthrosis, multiple sclerosis, atherosclerosis, sepsis/septic shock, dermal inflammation, graft rejection, and inflammation secondary to chemotherapy or radiotherapy of neoplastic disease.
- the present invention is presently believed to be particularly suitable for the treatment of arthritis and/or osteoarthrosis.
- Administration may proceed by oral, buccal, parenteral, topical, rectal, transdermal or intranasal administration, though oral administration is preferred.
- mammal is intended to include larger mammals such as humans as well as domestic or farm animals such as dogs, cats, horses, sheep, pigs, cattle, etc. Among these mammals, humans are particularly interesting subjects to benefit from the invention.
- Intake of fish oil rich in n-3 PUFA's is believed to result in a decrease in cell membrane arachidonic acid level and a concomitant decrease in the synthesis of eicosanoids (prostaglandins, thromboxanes and leucotriens) from arachidonic acid.
- eicosanoids prostaglandins, thromboxanes and leucotriens
- One of the mechanisms behind rheumatoid and osteoarthritic pain and stiffness, is a liberation of cytotoxic agents from neutrophils, which results in the destruction of tissue and the formation of oedema, resulting in pain.
- the number of neutrophils present influences the amount of tissue destructive components liberated.
- the migration (chemotaxis) of neutrophils as well as the ability of these leucocytes to liberate cytotoxic agents are therefore essential to the formation of pain and also to the degree of tissue destruction locally.
- Eicosanoids of interest to neutrophile function are the leucotriens. Intake of fish oil may decease the production of leucotriens and inhibit neutrophil function. In that way fish oil may act as an anti-inflammatory agent.
- fish oil may inhibit the proliferation of another group of white blood cells, the lymphocytes, as cytotoxic lymphocyte activity has been reported to be significantly diminished after intake of fish oil.
- Mechanisms behind the impact of fish oil on pain and stiffness in rheumatoid arthritis and osteoarthrosis therefore may be:
- Rose hip powder has also been tested in vitro using a modified boyden chamber. After the addition of even low doses of rose hip, neutrophil chemotaxis towards the chemotactic peptide f-Met-Leu-Phe and Zymosan was markedly reduced. Moreover, the oxidative burst from neutrophils, when using chemiluminescence, was abolished, indicating antioxidative properties. When chemotaxis and oxidative burst response were tested in humans taking rose hip powder, neutrophil chemotaxis and oxidative burst response significantly declined using even low concentrations of rose hip. It was also shown that in patients suffering from osteoarthrosis, pain significantly declined after four weeks of rose hip treatment.
- the isolated compound should be a potent inhibitor of the oxidative burst response of the human peripheral blood polymorphonuclear leukocytes, the most important and abundant inflammatory cells. It is therefore believed that the glycosides of mono- or diacylglycerol compounds, especially GOPO, are responsible for the anti inflammatory effects of rose hip extracts.
- eicosanoids such as prostaglandins, thromboxane and leucotriens, it is likely to also inhibit platelet aggregation.
- GOPO and fish oil, GOPO, fish oil and rose hip are complementary to each other and thus superior to fish oil or rose hip alone regarding the reduction of pain and stiffness in patients suffering from osteoarthrosis, as established by the above examples, and further may have prophylactic effects to prevent further disease progression.
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Abstract
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Application Number | Priority Date | Filing Date | Title |
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DKPA200801492 | 2008-10-30 | ||
PCT/DK2009/000227 WO2010048955A1 (en) | 2008-10-30 | 2009-10-28 | Composition comprising a glycoside of a mono- or diacyiglycerol compound and an oil rich in n-3 polyunsaturated fatty acids, a method of producing the composition and use of the composition |
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EP2349281A1 true EP2349281A1 (en) | 2011-08-03 |
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EP20090752271 Withdrawn EP2349281A1 (en) | 2008-10-30 | 2009-10-28 | Composition comprising a glycoside of a mono- or diacyiglycerol compound and an oil rich in n-3 polyunsaturated fatty acids, a method of producing the composition and use of the composition |
Country Status (3)
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US (1) | US20110257110A1 (en) |
EP (1) | EP2349281A1 (en) |
WO (1) | WO2010048955A1 (en) |
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Publication number | Priority date | Publication date | Assignee | Title |
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DK177605B1 (en) | 2010-03-16 | 2013-11-18 | Hyben Vital Licens Aps | Compositions of rose hips enriched with seeds of rose hips and their use as anti-inflammatory natural medicine for alleviating/reducing symptoms associated with inflammation and joint diseases such as arthritis and/or osteo-arthritis |
US8877259B2 (en) | 2012-02-09 | 2014-11-04 | Mary Kay Inc. | Cosmetic formulation |
PL2872135T3 (en) * | 2012-07-06 | 2017-04-28 | Orkla Health A/S | Process for the manufacture of rose hip powder |
GB201406172D0 (en) | 2014-04-04 | 2014-05-21 | Univ Nottingham | Therapy and pharmaceutical composition |
US10137108B2 (en) * | 2015-01-23 | 2018-11-27 | Nestec S.A. | Nutritional composition useful in the treatment of IBD patients |
Family Cites Families (8)
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DE19634019A1 (en) * | 1996-08-23 | 1998-02-26 | Beiersdorf Ag | Antimicrobial, antiviral, antiparasitic and antiprotozoal agents |
WO1998051315A1 (en) * | 1997-05-12 | 1998-11-19 | Nippon Shinyaku Co., Ltd. | Therapeutic agent for articular rheumatism |
US6024960A (en) | 1998-04-17 | 2000-02-15 | Otto Torbjorn Hansen And Marianne Hansen | Rose-hip formulations as anti-inflammatory natural medicine for alleviating/reducing symptoms associated with inflammation and arthritis |
JP2001346517A (en) * | 2000-06-02 | 2001-12-18 | K-Tac Planners Co Ltd | Edible fat and oil |
US6485752B1 (en) | 2000-10-23 | 2002-11-26 | Otto Torbjorn Hansen | Composition and method for alleviating joint pain and stiffness |
CN100469784C (en) * | 2001-11-21 | 2009-03-18 | 奥尔胡斯大学 | Use of glycosides of mono- and diacylglycerol as anti-inflammatory agents |
ATE524483T1 (en) | 2006-07-03 | 2011-09-15 | Hyben Vital Licens Aps | METHOD FOR PRODUCING A GLYCOSIDE OF A MONO- OR DIACYL-GLYCEROL PRODUCT FROM A PLANT MATERIAL |
JP2010526123A (en) * | 2007-05-08 | 2010-07-29 | ディーエスエム アイピー アセッツ ビー.ブイ. | Weight maintenance and body composition |
-
2009
- 2009-10-28 EP EP20090752271 patent/EP2349281A1/en not_active Withdrawn
- 2009-10-28 WO PCT/DK2009/000227 patent/WO2010048955A1/en active Application Filing
-
2011
- 2011-04-21 US US13/091,318 patent/US20110257110A1/en not_active Abandoned
Non-Patent Citations (13)
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"Bharata Bhaisajya Ratnakara", vol. I, 1999, pages: 26 |
AMINUDDAULAH ABUL FARJ IBN QUFF MASEEHI: "Kitaab-al-Umdah-fil-Jeraahat", vol. I, 1937, pages: 218 |
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See also references of WO2010048955A1 |
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WO2010048955A1 (en) | 2010-05-06 |
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